Interactions of organic anion transporters and organic cation transporters with mycotoxins

dc.contributor.authorKittipong Tachampaen_US
dc.contributor.authorMichio Takedaen_US
dc.contributor.authorSuparat Khamdangen_US
dc.contributor.authorRie Noshiro-Kofujien_US
dc.contributor.authorMinoru Tsudaen_US
dc.contributor.authorSurawat Jariyawaten_US
dc.contributor.authorToshiyuki Fukutomien_US
dc.contributor.authorSamaisukh Sophasanen_US
dc.contributor.authorNaohiko Anzaien_US
dc.contributor.authorHitoshi Endouen_US
dc.contributor.otherKyorin University School of Medicineen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherUbon Rajathanee Universityen_US
dc.description.abstractMycotoxins are secondary metabolites of moulds that which exert adverse effects in humans and animals. It is known that direct cellular toxicity is often associated with increased cellular accumulation of toxic compounds, and membrane transport may be the first fundamental stage in the development of the cytotoxicity. To elucidate the entry pathway for mycotoxins into cells, we have investigated the interactions of human and rat organic anion transporters (hOATs/rOats) and human organic cation transporters (hOCTs) with mycotoxins using cells stably expressing hOATs/rOats/hOCTs. The mycotoxins tested were aflatoxin B1, α-zearalenol, citrinin, citrioveridine, cyclopiazonic acid, fumonisin B1, gliotoxin, patulin, penicillic acid, rubratoxin B, and zearalenone. These mycotoxins inhibited organic anion uptake mediated by hOAT1-4, and organic cation uptake mediated by hOCT1-2. By comparing the IC 50 values of mycotoxins for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with mycotoxins than hOAT2 and hOAT4. There was no interspecies difference between humans and rats for the interactions of OATs with mycotoxins except that of OAT3 with rubratoxin B. Finally, we observed that hOAT1-4 and hOCT1-2 mediated the uptake of aflatoxin B1. In conclusion, hOATs and hOCTs interacted with various mycotoxins. Considering the localization of hOATs/rOats and hOCTs, it was suggested that these transporters were the possible entrance pathway for mycotoxins in kidney and liver, leading to the induction of adverse effects in humans and rats. ©2008 The Japanese Pharmacological Society.en_US
dc.identifier.citationJournal of Pharmacological Sciences. Vol.106, No.3 (2008), 435-443en_US
dc.rightsMahidol Universityen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleInteractions of organic anion transporters and organic cation transporters with mycotoxinsen_US